9TZM

Programmed cell death 1 ligand 1 with small molecule inhibitor ligand

This is a non-PDB format compatible entry.

Summary for 9TZM

• Entry DOI: 10.2210/pdb9tzm/pdb
• Descriptor: Programmed cell death 1 ligand 1, (2~{R})-2-[[2-[(5-cyanopyridin-3-yl)methoxy]-4-[[2-methyl-3-(3-methylselanylphenyl)phenyl]methoxy]phenyl]methylamino]-3-oxidanyl-propanoic acid (3 entities in total)
• Functional Keywords: pd-l1, smi, selenium, immunotherapy, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 27405.31

Authors

Plewka, J.,Magiera-Mularz, K.,Wen, Z.,Yanling, W.,Feng, Z.,Shenwei, Y.,Liang, Q.,Zheyu, C. (deposition date: 2026-01-23, release date: 2026-07-15)

Primary citation

Wang, J.,Yu, S.,Qian, L.,Plewka, J.,Ni, R.,Wang, C.,Zhang, F.,Chen, Z.,Awadasseid, A.,Wu, Y.,Magiera-Mularz, K.,Zhang, W.
Novel Selenium-Containing Small Molecule PD-L1 Inhibitors: Design, Synthesis, and Evaluation of the Antitumor Activity.
J.Med.Chem., 2026

PubMed Abstract: Novel selenium-containing small molecule PD-L1 inhibitors were designed and synthesized for the first time to explore their potential as antitumor agents. By computer-aided structural optimization, HTRF and SPR techniques, compound was identified as the most potent blocker of the PD-1/PD-L1 interaction, exhibiting an IC value of 5.2 ± 0.5 nM, a value of 9.06 ± 1.25 nM, respectively. Study on the /hPD-L1 cocrystal structure (2.9 Å) revealed a unique selenomethyl-involved binding mode, which may interpret its superior inhibitory activity compared to other analogs. Cell-based assays showed that can mediate the internalization of PD-L1 and strongly block hPD-1 and hPD-L1 interaction, demonstrating its effectiveness in biological events. Notably, in the Hu-PD-L1 MC38 mouse model, significantly inhibited tumor growth, with a tumor growth inhibition (TGI) rate of 77.79% (60 mg/kg, administrated intragastrically) with no observable toxicity. These data indicate that is a promising and safe novel antitumor agent worthy of further development.

PubMed: 42394434
DOI: 10.1021/acs.jmedchem.6c00363

Experimental method

X-RAY DIFFRACTION (2.901 Å)